RT Journal Article
T1 Metabolomics of the tryptophan-kynurenine degradation pathway and risk of atrial fibrillation and heart failure: potential modification effect of Mediterranean diet.
A1 Razquin, Cristina
A1 Ruiz-Canela, Miguel
A1 Toledo, Estefania
A1 Hernández-Alonso, Pablo
A1 Clish, Clary B
A1 Guasch-Ferré, Marta
A1 Li, Jun
A1 Wittenbecher, Clemens
A1 Dennis, Courtney
A1 Alonso-Gómez, Angel
A1 Fitó, Montse
A1 Liang, Liming
A1 Corella, Dolores
A1 Gómez-Gracia, Enrique
A1 Estruch, Ramon
A1 Fiol, Miquel
A1 Lapetra, Jose
A1 Serra-Majem, Lluis
A1 Ros, Emilio
A1 Aros, Fernando
A1 Salas-Salvadó, Jordi
A1 Hu, Frank B
A1 Martínez-González, Miguel A
K1 Mediterranean diet
K1 PREDIMED
K1 atrial fibrillation
K1 case–control
K1 heart failure
K1 kynurenine
K1 metabolomics
K1 tryptophan
AB The tryptophan-kynurenine pathway is linked to inflammation. We hypothesize that metabolites implicated in this pathway may be associated with the risk of heart failure (HF) or atrial fibrillation (AF) in a population at high risk of cardiovascular disease. We aimed to prospectively analyze the associations of kynurenine-related metabolites with the risk of HF and AF and to analyze a potential effect modification by the randomized interventions of the PREDIMED (Prevención con Dieta Mediterránea) trial with Mediterranean diet (MedDiet). Two case-control studies nested within the PREDIMED trial were designed. We selected 324 incident HF cases and 502 incident AF cases individually matched with ≤3 controls. Conditional logistic regression models were fitted. Interactions with the intervention were tested for each of the baseline plasma metabolites measured by LC-tandem MS. Higher baseline kynurenine:tryptophan ratio (OR for 1 SD: 1.20; 95% CI: 1.01, 1.43) and higher levels of kynurenic acid (OR: 1.19; 95% CI: 1.01, 1.40) were associated with HF. Quinolinic acid was associated with AF (OR: 1.15; 95% CI: 1.01, 1.32) and HF (OR: 1.25; 95% CI: 1.04, 1.49). The MedDiet intervention modified the positive associations of kynurenine (Pinteraction = 0.006), kynurenic acid (Pinteraction = 0.008), and quinolinic acid (Pinteraction = 0.033) with HF and the association between kynurenic acid and AF (Pinteraction = 0.02). We found that tryptophan-kynurenine pathway metabolites were prospectively associated with higher HF risk and to a lesser extent with AF risk. Moreover, an effect modification by MedDiet was observed for the association between plasma baseline kynurenine-related metabolites and the risk of HF, showing that the positive association of increased levels of these metabolites and HF was restricted to the control group.
YR 2021
FD 2021
LK https://hdl.handle.net/10668/26962
UL https://hdl.handle.net/10668/26962
LA en
DS RISalud
RD Apr 8, 2025